These studies compared the dose-response effects of oral vs. transdermal selegiline on antidepressant-like activity and brain monoamine oxidase (MAO) activities in rats. Rats received selegiline by gavage (0-100 mg/kg) or via transdermal patches (0-4.8 cm2, 0-8.7 mg/kg) daily for 7 days; antidepressant-like activity was determined using the forced-swim test. Following behavioral testing, cerebral cortices were assayed for MAO-A and MAO-B activities. Doses of selegiline that selectively inhibited MAO-B (3 and 10 mg/kg/day by gavage and 0.4 mg/kg/day via patch) did not alter either immobility or latency time. However, the oral administration of 30 or 100 mg/kg/day or the transdermal administration of 8.7 mg/kg/day, doses that led to greater than 70% inhibition of MAO-A, decreased immobility time significantly. The IC50s for inhibition of MAO-A following oral and transdermal administration for 7 days were 19.8 and 1.1 mg/kg, respectively. Results indicate that both oral and transdermal selegiline have antidepressant-like activity as assessed by the forced-swim test, and that transdermal administration, which bypasses first-pass metabolism, allows for using lower doses than oral administration.